1. Field of the Invention
The present invention relates generally to the fields of cancer, immunology and immunotherapy. More particularly, it concerns the therapeutic use of anti-CD26 antibodies, including monoclonal, humanized, and polyclonal anti-CD26 antibodies, for the prevention and treatment of cancers and immune diseases. Various modes of administration, and doses are described.
2. Description of Related Art
Cancer has become one of the leading causes of death in the western world, second only behind heart disease. Current estimates project that one person in three in the U.S. will develop cancer, and that one person in five will die from cancer. Currently, there are few effective options for the treatment of cancer. The most conventional options of cancer treatment are surgery, radiation therapy and chemotherapy. Typically, surgical methods are used for the diagnosis (by surgical biopsy) and treatment of cancer (surgery to remove cancerous growths). However, if the cancer has metastasized and is widespread, surgery is unlikely to result in a cure and an alternate approach must be taken. Radiation therapy and chemotherapy are other forms of cancer treatments. However, both radiation therapy and chemotherapy being systemic therapies are associated with numerous side effects since normal cells are also affected. Side effects of the currently used cancer therapies include skin irritation, difficulty swallowing, dry mouth, nausea, diarrhea, hair loss, mouth sores, fatigue, bleeding to name a few. Thus, major challenges remain to be overcome for cancer therapy.
Target-directed therapies, such as those using specific antibodies as therapeutic agents, offers advantages over the non-targeted therapies such as systemic chemotherapy via oral or intravenous administration of drugs or radiation therapy. There are two types of antibody-based therapies. The more common type is to identify a tumor antigen (i.e., a protein expressed on tumors and cancer cells and not in normal tissues) and develop an antibody, preferably a monoclonal antibody (mAb) directed to the tumor antigen. One can then conjugate any therapeutic agent, such as a chemotherapeutic agent, a radionuclide, modified toxin, etc., to this antibody to achieve targeted therapy by the therapeutic agent to the tumor. The other kind of antibody based therapy is by providing an antibody which in itself has therapeutic properties against the tumor/cancer cells it targets. The added advantage of this second form of antibody-based therapy is that one may additionally conjugate another therapeutic agent to the therapeutic antibody to achieve a more effective treatment.
The major advantage with any antibody-directed therapy, and of therapy using monoclonal antibodies (mAbs) in particular, is the ability to deliver increased doses of a therapeutic agent to a tumor, with greater sparing of normal tissue from the side effects of the therapeutic agent. Despite the identification of several antibodies for cancer therapies, there is still a need to identify new and more effective therapeutic antibodies to provide therapy for various cancer types.
A membrane protein, CD26, associated with numerous immune-related functions, is known to be expressed on the surface of several human cancers, particularly cancers that are in advanced stages and hence, associated with poor patient prognosis. For example, lung adenocarcinomas are positive for the enzymatic activity of CD26 while other histological types of lung carcinomas are negative for CD26 activity (Asada et al., 1993); CD26 expression is high in differentiated thyroid carcinomas and absent in benign thyroid diseases (Tanaka et al., 1995); high levels of CD26 protein and mRNA expression are found in B-chronic lymphocytic leukemia cells (Bauvois et al, 1999); and CD26 expression is high in aggressive T-cell malignancies, such as T-cell lymphoblastic lymphomas/acute lymphoblastic leukemias (LBL/ALL), T-cell CD30+ anaplastic large cell lymphomas. These cancer types are difficult to treat as they are particularly resistant to current treatment modalities. There is a great need to find therapies that would be useful in treating and preventing such aggressive diseases.